Skin hyper-pigmentation comes of various origins such as the hormonal disorder followed by the inflammatory response of skin, genetic disease and ultraviolet irradiation, mainly the synthetic disorder and distribution disorder of melanin pigment, which results in skin discoloration, freckles, skin darkening after skin inflammation, purpura senile and so on.
The main function of melanin is to scavenge oxygen radical, which can protect skin from the injury. Therefore, it has been known that the plenty of melanin shows potent response on skin system for protecting skin from physical or chemical toxic substance. Melanin is formed by serial step i.e., converting tyrosine to dopaquinone by tyrosinase enzyme followed by further enzymatic reaction and spontaneous oxidative reaction and so on. Therefore, the inhibiting methods of melanin biosynthesis for protecting skin tanning are classified by follows: (1) LTV protecting method to get rid of the main cause of melanin formation, which is expected to give satisfactory results (2) Inhibiting method of core carbohydrate biosynthesis necessary to tyrosinase activity (3) Inhibiting method of the function of tyrosinase enzyme participating in melanin formation using kojic acid or arbutin (4) Inhibiting method of cell differentiation, using hydroquinone which has specific toxicity on melanocyte, melanin forming cell (5) De-colorizing method by reducing melanin formation.
In order to inhibit melanin biosynthesis, various skin-whitening materials such as hydroquinone, arbutin, ascorbic acid, kojic acid, and the extract of natural herb etc have been used till now. However, those conventionally available skin-whitening substances have several problems, for example; hydroquinone shows limit to use because of its sensitivity to skin, unfavorable staining or odor etc; ascorbic acid is easily oxidized under oxygen in the air, which results in unfavorable staining and odor of cosmetic preparation; herb extract is difficult to maintain its homogeneity and efficacy because of its various resources in spite of its strong skin whitening effect.
Besides the above-described skin-whitening materials, other skin-whitening substances have been developed recently as follows: for example, Korean Patent registration No. 509848 discloses skin-whitening cosmetic composition comprising khellactone derivatives isolated from Peucedanum praeruptorum as an active ingredient; and Korean Patent registration No. 479741 discloses skin-whitening cosmetic composition comprising glucose acylated derivatives as an active ingredient and so on. However those materials show several problems such as low-yield preparation etc.
Therefore, the present inventors have endeavored to find chemical compounds showing potent skin-whitening activity and finally found new cyclic derivatives showing various advantageous properties such as potent inhibiting effect on melanin formation and skin hyper-pigmentation activity with no adverse response to skin, or easiness to mass-production synthesis etc in the present invention.